Cancer Vaccines for Triple-Negative Breast Cancer: A Systematic Review.

Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the poorest outcomes, and is associated with a high risk of relapse and metastasis. The treatment choices for this malignancy have been confined to conventional chemotherapeutic agents, due to a lack of expression of the canonical molecular targets. Immunotherapy has been recently changing the treatment paradigm for many types of tumors, and the approach of evoking active immune responses in the milieu of breast tumors through cancer vaccines has been introduced as one of the most novel immunotherapeutic approaches. Accordingly, a number of vaccines for the treatment or prevention of recurrence have been developed and are currently being studied in TNBC patients, while none have yet received any approvals. To elucidate the efficacy and safety of these vaccines, we performed a systematic review of the available literature on the topic. After searching the PubMed, Scopus, Web of Science, Embase, Cochrane CENTRAL, and Google Scholar databases, a total of 5701 results were obtained, from which 42 clinical studies were eventually included based on the predefined criteria. The overall quality of the included studies was acceptable. However, due to a lack of reporting outcomes of survival or progression in some studies (which were presented as conference abstracts) as well as the heterogeneity of the reported outcomes and study designs, we were not able to carry out a meta-analysis. A total of 32 different vaccines have so far been evaluated in TNBC patients, with the majority belonging to the peptide-based vaccine type. The other vaccines were in the cell or nucleic acid (RNA/DNA)-based categories. Most vaccines proved to be safe with low-grade, local adverse events and could efficiently evoke cellular immune responses; however, most trials were not able to demonstrate significant improvements in clinical indices of efficacy. This is in part due to the limited number of randomized studies, as well as the limited TNBC population of each trial. However, due to the encouraging results of the currently published trials, we anticipate that this strategy could show its potential through larger, phase III randomized studies in the near future.

Fiber manipulation and post-assembly nanobody conjugation for adenoviral vector retargeting through SpyTag-SpyCatcher protein ligation.

For adenoviruses (Ads) to be optimally effective in cancer theranostics, they need to be retargeted toward target cells and lose their natural tropism. Typically, this is accomplished by either engineering fiber proteins and/or employing bispecific adapters, capable of bonding Ad fibers and tumor antigen receptors. This study aimed to present a simple and versatile method for generating Ad-based bionanoparticles specific to target cells, using the SpyTag-SpyCatcher system. The SpyTag peptide was inserted into the HI loop of fiber-knob protein, which could act as a covalent anchoring site for a targeting moiety fused to a truncated SpyCatcher (SpyCatcherΔ) pair. After confirming the presence and functionality of SpyTag on the Ad type-5 (Ad5) fiber knob, an adapter molecule, comprising of SpyCatcherΔ fused to an anti-vascular endothelial growth factor receptor 2 (VEGFR2) nanobody, was recombinantly expressed in Escherichia coli and purified before conjugation to fiber-modified Ad5 (fmAd5). After evaluating fmAd5 detargeting from its primary coxsackie and adenovirus receptor (CAR), the nanobody-decorated fmAd5 could be efficiently retargeted to VEGFR2-expressing 293/KDR and human umbilical vein endothelial (HUVEC) cell lines. In conclusion, a plug-and-play platform was described in this study for detargeting and retargeting Ad5 through the SpyTag-SpyCatcher system, which could be potentially applied to generate tailored bionanoparticles for a broad range of specific targets; therefore, it can be introduced as a promising approach in cancer nanotheranostics.

Comparison of polyacrylate polyalcohol copolymer (PPC) and dextranomer/hyaluronic acid (Dx/HA) for treatment of vesicoureteral reflux. A systematic review and meta-analysis.

PURPOSE: Our study aimed to compare the efficacy of polyacrylate polyalcohol copolymer and Dextranomer-Hyaluronic Acid for endoscopic treatment of vesicoureteral reflux. MATERIAL AND METHODS: MEDLINE, EMBASE, Scopus, Web of science, Ovid, Cochrane databases, Google scholar have been searched for studies published until January 2022 in any language. Studies that compared the success rate for endoscopic treatment of vesicoureteral reflux in children with two bulking agents, namely, "polyacrylate polyalcohol copolymer." and "Dextranomer-Hyaluronic Acid" were included for this analysis. RESULTS: Nine studies were included in data synthesis for this meta-analysis. Pooled data with a total of 763 ureters in PPC group and 718 ureters in Dx/HA group indicated that ureters in PPC group were more likely to undergo complete reflux resolution than Dx/HA (OR 3.80, 95% CI: 2.71; 5.31). Among subgroup of patients with high grade reflux, PPC injection had more resolution rate compared to Dx/HA patients (OR: 2.92, 95% CI: 1.19-7.16). In total, 95.81% of the PPC group and 86.52% of the Dx/HA group experienced success after the third injection. However a concerning complication of endoscopic treatment which is ureterovesical junction obstruction (UVJO) was more prevalent in PPC group. So the possible benefits arising from endoscopic treatment with PPC could be offset by the costs of re-implantation surgery or stenting in the case of UVJO. CONCLUSION: These data indicate that PPC injection for vesicoureteral reflux treatment was associated with a higher success rate, but concerningly, UVJO incidence was higher in the PPC group which might negate the possible benefits of PPC injection However, due to the lack of studies with long-term follow-up, we couldn't reach a definitive conclusion about the superiority of one of the bulking agents over the other.

Efficacy of Topical Losartan in Management of Mammoplasty and Abdominoplasty Scars: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Annually, millions of people suffer from skin scars' psychological and physical disadvantages. Pathologic scars prevention is challenging and requires developing feasible and effective therapeutic strategies. Regarding promising results of losartan (an angiotensin 1 receptor inhibitor) on skin scar in preclinical studies, we aimed to assess the losartan ointment's impact on surgical scars in a clinical setting. MATERIAL AND METHOD: Twenty-four patients with surgical wounds were enrolled from Razi hospital's plastic and reconstructive surgery department. The patients were trained to apply ointments 14-18 days post-surgery on the determined scar side, twice a day for 6 months. Two dermatologists independently evaluated scar formation at 3 and 6-month follow-ups using the Vancouver Scar Scale (VSS) score. RESULT: Twenty-four female patients with cosmetic surgeries were included. The mean VSS score of losartan-treated sides was 7.1 ± 2.06 (at month 3) and 5.21 ± 1.71 (at month 6) that significantly were different from placebo-treated sides (9.77 ± 1.55 and 8.31 ± 1.88 at 3 and 6 months, respectively) (P value < 0.001 and < 0.001, respectively, for months 3 and 6). The subset analysis demonstrated a significant improvement in height (P value < 0.001 at 3 and 6 months), pliability (P value < 0.001 at 3 and 6 months), and vascularity (P value < 0.001 at 3 and 6 months) subsets at losartan compared to placebo-treated side. Losartan ointment was well tolerated with no complication. CONCLUSION: Losartan ointment successfully improved scar formation in mammoplasty and abdominoplasty patients. The losartan preventive effect should be confirmed in future large-scale studies with long-term follow-ups. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Clinical and Laboratory Predictors of Severity, Criticality, and Mortality in COVID-19: A Multisystem Disease.

Coronavirus disease 2019 (COVID-19) pandemic continues devastating effects on healthcare systems. Such a crisis calls for an urgent need to develop a risk stratification tool. The present chapter aimed to identify laboratory and clinical correlates of adverse outcomes in patients with COVID-19. To this end, we conducted a systematic evaluation of studies that investigated laboratory abnormalities in patients with COVID-19 and compared i. patients with a severe form of disease and patients with a non-severe form of the disease, ii. patients who were in critical condition and patients who were not in critical condition, and iii. patients who survived and patients who died. We included 54 studies in the data synthesis. Compared to patients with a non-severe form of COVID-19, patients who had a severe form of disease revealed higher values for white blood cells (WBC), polymorphonuclear leukocytes (PMN), total bilirubin, alanine aminotransferase (ALT), creatinine, troponin, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. By contrast, platelet count, lymphocyte count, and albumin levels were decreased in patients with a severe form of COVID-19. Also, patients with a severe phenotype of disease were more likely to have diabetes, chronic heart disease, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, hypertension, chronic kidney disease (CKD), and malignancy. Compared to patients who survived, patients who died had higher WBC, PMN, total bilirubin, ALT, procalcitonin, IL-6, creatinine, PT, lymphocyte count, platelet count, and albumin. Also, non-survivors revealed a higher prevalence of diabetes, chronic heart disease, COPD, cerebrovascular disease, and CKD. Meta-analyses identified several laboratory parameters that might help the prediction of severe, critical, and lethal phenotypes of COVID-19. These parameters correlate with the immune system function, inflammation, coagulation, and liver and kidney function.

Brucella Pneumonia with Systemic Complications and Pancytopenia: A Case Report.

BACKGROUND: Iran, which is regarded as an endemic region for brucellosis, ranks second in brucella prevalence in the world. Pulmonary involvement is a rare complication of brucellosis. In this article, we aimed to report a case of systemic brucellosis complicated with brucella pneumonia. ; Case Presentation: A 39-years-old man was referred to the emergency department with weakness, productive coughs and severe weight loss during 8 months. Agglutination tests for brucellosis showed high titers suggestive for brucella infection. After 6 days of treatment, the patients' clinical state improved significantly. ; Conclusion: The patient had systemic signs and bone marrow suppression with pulmonary involvement that his diagnosis confirmed with delay after one year, but with treatment, he had a very good outcome.

Targeted therapy strategies against SARS-CoV-2 cell entry mechanisms: A systematic review of in vitro and in vivo studies.

Due to the rapidly spreading of novel coronavirus disease (COVID-19) worldwide, there is an urgent need to develop efficient vaccines and specific antiviral treatments. Pathways of the viral entry into cells are interesting subjects for targeted therapy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The present study aims to provide a systematic evaluation of the most recent in vitro and in vivo investigations targeting SARS-CoV-2 cell entry. A systematic search was carried out in major medical sources, including MEDLINE (through PubMed), Web of Science, Scopus, and EMBASE. Combinations of the following search terms were used: SARS-CoV-2, in vitro, in vivo, preclinical, targeted therapy, and cell entry. A modified version of the Consolidated Standards of Reporting Trials and Systematic Review Centre for Laboratory Animal Experimentation assessment tools were applied for evaluating the risk of bias of in vitro and in vivo studies, respectively. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. A total of 2,649 articles were identified through searching PubMed, Web of Science, Scopus, EMBASE, Google Scholar, and Biorxiv. Finally, 22 studies (one in vivo study and 21 in vitro studies) were included. The spike (S) glycoprotein of the SARS-CoV-2 was the main target of investigation in 19 studies. SARS-CoV-2 can enter into the host cells through endocytosis or independently. SARS-CoV-2 S protein utilizes angiotensin-converting enzyme 2 or CD147 as its cell-surface receptor to attach host cells. It consists of S1 and S2 subunits. The S1 subunit mediates viral attachment to the host cells, while the S2 subunit facilitates virus-host membrane fusion. The cleavage of the S1-S2 protein, which is required for the conformational changes of the S2 subunit and processing of viral fusion, is regulated by the host proteases, including cathepsin L (during endocytosis) and type II membrane serine protease (independently). Targeted therapy strategies against SARS-CoV-2 cell entry mechanisms fall into four main categories: strategies targeting virus receptors on the host, strategies neutralizing SARS-CoV-2 spike protein, strategies targeting virus fusion to host cells, and strategies targeting endosomal and non-endosomal dependent pathways of virus entry. Inhibition of the viral entry by targeting host or virus-related components remains the most potent strategy to prevent and treat COVID-19. Further high-quality investigations are needed to assess the efficacy of the proposed targets and develop specific antivirals against SARS-CoV-2.

Seasonal and gender variation in skin disease: A cross-sectional study of 3120 patients at Razi hospital.

Objective: We aimed to determine the prevalence of different skin diseases and their seasonal variations at the Razi dermatology hospital from 2019 to 2020. Methods: In this cross-sectional study, we obtained data from the medical records of 3120 patients visiting the dermatology clinic of Razi hospital. The prevalence of skin diseases was evaluated using meteorologically defined seasons. We looked for significant equally distributed results during each season. Results: During all seasons, women were referred to our clinic more frequently than men. Some diseases demonstrated significant seasonality with a peak during the winter, including acne, eczema, wart, seborrheic dermatitis, nevus, vitiligo, lentigo, and dermatophytosis. Atopic dermatitis was more frequent during the spring and winter compared with other seasons (p < .05). Actinic keratosis and lichen planus showed a significant seasonal trend with a peak during the summer (p < .05). Infections, including viral, bacterial, and fungal skin diseases, were more frequent during the winter than the summer (p = .001). Conclusion: This study provides an overview of the seasonal distribution of dermatology visits at our referral hospital, which will aid in developing better policies to prevent and manage skin disorders in outpatient visits.

Neurological recovery following traumatic spinal cord injury: a systematic review and meta-analysis.

OBJECTIVEPredicting neurological recovery following traumatic spinal cord injury (TSCI) is a complex task considering the heterogeneous nature of injury and the inconsistency of individual studies. This study aims to summarize the current evidence on neurological recovery following TSCI by use of a meta-analytical approach, and to identify injury, treatment, and study variables with prognostic significance.METHODSA literature search in MEDLINE and EMBASE was performed, and studies reporting follow-up changes in American Spinal Injury Association (ASIA) Impairment Scale (AIS) or Frankel or ASIA motor score (AMS) scales were included in the meta-analysis. The proportion of patients with at least 1 grade of AIS/Frankel improvement, and point changes in AMS were calculated using random pooled effect analysis. The potential effect of severity, level and mechanism of injury, type of treatment, time and country of study, and follow-up duration were evaluated using meta-regression analysis.RESULTSA total of 114 studies were included, reporting AIS/Frankel changes in 19,913 patients and AMS changes in 6920 patients. Overall, the quality of evidence was poor. The AIS/Frankel conversion rate was 19.3% (95% CI 16.2-22.6) for patients with grade A, 73.8% (95% CI 69.0-78.4) for those with grade B, 87.3% (95% CI 77.9-94.8) for those with grade C, and 46.5% (95% CI 38.2-54.9) for those with grade D. Neurological recovery was significantly different between all grades of SCI severity in the following order: C > B > D > A. Level of injury was a significant predictor of recovery; recovery rates followed this pattern: lumbar > cervical and thoracolumbar > thoracic. Thoracic SCI and penetrating SCI were significantly more likely to result in complete injury. Penetrating TSCI had a significantly lower recovery rate compared to blunt injury (OR 0.76, 95% CI 0.62-0.92; p = 0.006). Recovery rate was positively correlated with longer follow-up duration (p = 0.001). Studies with follow-up durations of approximately 6 months or less reported significantly lower recovery rates for incomplete SCI compared to studies with long-term (3-5 years) follow-ups.CONCLUSIONSThe authors' meta-analysis provides an overall quantitative description of neurological outcomes associated with TSCI. Moreover, they demonstrated how neurological recovery after TSCI is significantly dependent on injury factors (i.e., severity, level, and mechanism of injury), but is not associated with type of treatment or country of origin. Based on these results, a minimum follow-up of 12 months is recommended for TSCI studies that include patients with neurologically incomplete injury.